Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA)

Condition(s) targeted: Urethritis

Intervention: Azithromycin (Drug); Doxycycline (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Washington

Overall contact:
Lisa E. Manhart, PhD, Phone: (206) 744-3646, Email: lmanhart@u.washington.edu

The purpose of this study is to find out which of 2 different antibiotics, doxycycline or azithromycin, works best against germs that may cause nongonococcal urethritis. Study participants will include approximately 1200 men, 16 years of age or older, attending a sexually transmitted diseases clinic in Seattle, Washington with clinical signs of urethral inflammation (>5PMNs/HPF on a Gram-stained slide prepared from urethral exudates and/or a visible urethral discharge upon examination). Urine specimens will be collected and tested for Mycoplasma genitalium and Ureaplasmas. Each participant will receive a blinded packet of study medication. Participants will answer an enrollment questionnaire and will also receive a log to complete between visits to record information about treatment adherence, side effects, symptoms, and sexual activity. Men who are positive for M. genitalium and/or Ureaplasmas will be asked to complete two follow-up study visits. These visits will be scheduled for approximately 3 and 6 weeks after the initial visit. During follow-up visits, participants will answer a follow-up questionnaire and will be re-evaluated for signs of urethritis and re-tested for M. genitalium and Ureaplasmas. Study participants with signs of urethritis or who test positive for M. genitalium or Ureaplasmas at the follow-up study visit will receive another blinded treatment packet containing the alternate medication. Those who require additional treatment at the 6-week visit will be asked to return for a fourth follow-up study visit at 9-10 weeks.

Official title: Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA): A Randomized Double-Blinded Treatment Trial to Assess the Efficacy of Azithromycin and Doxycycline for Clinical and Microbiological Cure of M. Genitalium in Men With Nongonococcal Urethritis

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Primary outcome: Eradication of M. genitalium or Ureaplasmas at first follow-up study visit

Secondary outcome:

Minimum inhibitory concentrations (MIC) of all cultivable strains of M. genitalium and Ureaplasmas

Clinical cure as measured by the absence of recurrent or persistent signs and/or symptoms of urethral infection among case subjects who were positive for M. genitalium or Ureaplasmas at the initial study visit

Detailed description: OBJECTIVES

The primary objective of this study is to determine the relative effectiveness of azithromycin and doxycycline in eradicating Mycoplasma genitalium and Ureaplasmas among men with nongonococcal urethritis (NGU).

Secondary objectives of this study are to:

- determine the sensitivity of persisting organisms to azithromycin and doxycycline by

performing minimum inhibitory concentration (MIC) testing

- determine the relationship between persistence/recurrence of clinical signs and

persistent/recurrent detection of M. genitalium and Ureaplasmas among men with NGU treated with azithromycin or doxycycline, measured by follow-up clinical exams and repeated assays performed on specimens collected at follow-up study visits

STUDY DESCRIPTION

1200 men with NGU, ages 16 and older, will be enrolled in a randomized double-blinded treatment trial. Urine samples, oral swabs, and urethral swabs will be obtained from each subject at the initial clinic visit. Urine specimens will be tested for M. genitalium and Ureaplasma. Study participants will be randomly assigned to receive one of two pre-packaged treatments: active doxycycline plus placebo azithromycin or active azithromycin plus placebo doxycycline. Subjects will complete a questionnaire, and will be given a simple standardized log in which they will be asked to keep track of adherence to the study drug, record solicited adverse events, note when symptoms disappear and/or reappear, and document sexual activity between study visits.

Subjects who test positive for M. genitalium or Ureaplasmas at the initial clinic visit will be asked to return for at least two follow-up study visits: at approximately 3 and 6 weeks following the initial clinic visit. During follow-up visits, participants will answer a follow-up questionnaire and will be re-evaluated for signs of urethritis and re-tested for M. genitalium and Ureaplasmas. Study participants with signs of urethritis or who test positive for M. genitalium or Ureaplasmas at the follow-up study visits will receive a blinded treatment packet containing the alternate medication, or open-label moxifloxacin if the alternate treatment regimen was administered at the prior follow-up study visit. If additional treatment is administered at the 6-week follow-up study visit, a fourth study visit will be scheduled to occur approximately 9 or 10 weeks following the initial clinic visit.

Study participants who were negative for M. genitalium and Ureaplasma at enrollment will be asked to return for evaluation for a single follow-up study visit, approximately 3 weeks after the initial clinic visit. At this visit they will complete the follow-up questionnaire and provide specimens for future testing.

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Has a visible urethral discharge or greater than or equal to 5 polymorphonuclear

leukocytes (PMNs) per high power field on a Gram-stained slide of a urethral swab sample

- Possesses and is willing to disclose valid contact information for follow-up

- English-speaking

- Gives informed consent

- Exhibits understanding of study procedures

- Exhibits ability to comply with study procedures for the entire length of the study

Exclusion Criteria:

- Has previously participated in this study

- Has taken antibiotics within the prior month

- Has known allergies to tetracyclines or azithromycin

- Is being treated with warfarin

Lisa E. Manhart, PhD, Phone: (206) 744-3646, Email: lmanhart@u.washington.edu

Public Health -- Seattle & King County Sexually Transmitted Diseases Clinic located at Harborview Medical Center, Seattle, Washington 98104, United States; Recruiting
Lisa E. Manhart, PhD, Principal Investigator
Matthew R. Golden, MD, MPH, Sub-Investigator
Patricia A. Totten, PhD, Sub-Investigator
George E. Kenny, PhD, Sub-Investigator

Starting date: January 2007
Ending date: August 2010
Last updated: August 26, 2008